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The Molecules’ Marathon

The Molecules’ Marathon

The benefits of exercise are not a surprise, and most of us have a fair sense of individual fitness. A recent article published in the Cell Journal1 went a step further and investigated what happens to the body at a molecular level after physical activity.

Researchers at Stanford School of Medicine examined the molecular responses to exercise in healthy individuals and in those with a risk of cardiometabolic disease. Thirty-six participants, aged between 40 and 75 years, were tested for cardiorespiratory fitness and oxygen consumption. Additionally, sixteen people were selected for the control experiment to understand the natural changes in the analytes in the absence of physical activity.

Understanding such details could be relevant amidst the current epidemic of diabetes and obesity. The team identified molecular markers from various processes such as lipid metabolism, oxidative stress, immunity, and cardiovascular activity.  In this article, however, we will highlight only the changes associated with the metabolisation of lipids and the production of hormones before and after exercise.

Changes in lipids

More than 700 lipids were examined in this study. Since these biomolecules are known to store energy, complex lipids such as glycerol phospholipids, sphingolipids and sterol lipids were taken into consideration.

At a resting state, glycerol lipids are one of the molecules that varies the most amongst people. Since muscle fibres are already rich in these lipids, this high variability suggests that glycerol phospholipids were actively metabolised. Researchers also observed an increased abundance of fatty acid esters, like acylcarnitines, which suggests that fats are metabolised to release energy.

Fatty Acids

Longer chain fatty acids were oxidised and showed a transient increase after exercise2, pointing out that these molecules may compensate for inflammation or signalling. In contrast, fatty acids with shorter and saturated carbons were preferred for energy production3. However, the level of these molecules in the insulin-resistant participants remained low, suggesting an abnormal fatty acid utilisation in their bodies.

Changes in hormones

Exercise stimulated the secretion of steroid and thyroid hormones, small chemicals produced by the steroid glands (the adrenal cortex, testes, and ovaries), and by the thyroid glands, respectively, that help to keep the body in balance. Corticosteroids, a particular class of steroid hormones that lowers inflammation, was also produced and released into the body after exercise.

Cortisol and insulin

Researchers also found that exercise stimulated the secretion of cortisol, a steroid hormone that is produced from cholesterol. In conditions of stress, this “fight-or-flight” hormone prepares the body for a response, flooding the bloodstream with sugars to produce energy4. Additionally, researchers saw a positive correlation between insulin and glucose levels. These two molecules go hand-in-hand to meet the energy demands of the body.

Leptin and ghrelin

The comprehensive analysis performed by the Stanford team also involved the metabolic hormones leptin and ghrelin, suggesting a role of exercise in appetite stimulation. Prior studies have shown that both these hormones decrease following bouts of intense exercise, thereby suppressing hunger5. Ghrelin and leptin differed with high and low variability, respectively, although at the resting state their levels were similar.

This is one of the first studies which thoroughly analysed the effects of exercise at a molecular level. However, it still has its limitations. The participating group was relatively small and mostly comprised an older layer of the population with varying BMI (body index mass) and insulin resistance status.

The future steps are underway which include large initiatives by Molecular Transducers of Physical Activity Consortium. The plan is to scale the concepts presented here with muscle and fat biopsy samples1.

1. Contrepois, Kévin, et al. “Molecular Choreography of Acute Exercise.” Cell 181.5 (2020): 1112-1130.
2. Calder, Philip C., et al. “A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.” British Journal of Nutrition 109.S1 (2013): S1-S34.
3. Ranallo, Romolo F., and Edward C. Rhodes. “Lipid metabolism during exercise.” Sports Medicine 26.1 (1998): 29-42.
4. Kjær, Michael. “Adrenal medulla and exercise training.” European journal of applied physiology and occupational physiology 77.3 (1998): 195-199.
5. King, N. A., V. J. Burley, and J. E. Blundell. “Exercise-induced suppression of appetite: effects on food intake and implications for energy balance.” European journal of clinical nutrition 48.10 (1994): 715-724.

Antara Mazumdar